Abstract 2977 Biology and therapeutic targeting of cohesin mutations in myeloid malignancies

Cohesin mutations are early but not initiating lesions in the transformation of hematopoietic stem and progenitor cells (HSPCs) to myelodysplastic syndrome (MDS) and acute myeloid leukemia, and they are thought to arise at the stage of clonal hematopoiesis of indeterminate potential, an age-associated clonal expansion of mutant HSPCs. Normal cohesin function is essential for proper sister chromatid cohesin, chromatin organization, DNA damage repair, and transcriptional regulation. Of note, the cohesin subunit STAG2 is one of only 12 human genes to be significantly mutated in four or more distinct types of cancer.